Not applicable.
The use of soluble viral receptors to prevent viral infection is being actively pursued. Amongst these efforts, intranasal administration of soluble ICAM-1 is being tested to prevent rhinovirus (cold) infection (Boehringer Ingelheim and Bayer). Soluble viral receptors are designed to work by engaging all host binding sites of a virus, thereby leaving none for the virus to attach to its target cell. However, a single viral particle has numerous binding sites for the host cell on its surface, e.g. rhinovirus has 60. Soluble viral receptors must simultaneously coat all binding sites on the virus to render it non-infectious. This requires an extremely high ratio of soluble viral receptors to viral particles (e.g.  greater than 60:1 for rhinovirus). Furthermore, since binding is a reversible process, it is unlikely that all binding sites on a virus could be coated simultaneously. Theoretically, even one free binding site on a virus would still allow it to be infectious to the host.
Clinical trials with soluble viral receptors to prevent viral infection have been met with limited success. Soluble ICAM-1 receptors were found to be only minimally effective in preventing cold infections, and only if they were already present on the nasal mucosa at the time of encounter with rhinovirus. Since an infected host is unaware of any symptoms until 2 to 3 days after an infection occurs, the only way to ensure that soluble viral receptors are present on the nasal mucosa at the time of infection is to apply them regularly throughout a period of presumed risk.
In particular, there is a problem of the short half-life of the soluble viral receptors on the mucosal surface. Since soluble viral receptors are freely mobile, they can be easily washed out by the normal mucociliary clearance mechanisms. This translates into a need for frequent reapplications. Subjects in the ICAM study had to apply the soluble viral receptors six times per day. This will likely translate into high cost and poor compliance, making soluble ICAM-1 receptor therapy an impractical approach for preventing cold infections.
The purpose of this invention is to improve the half-life of soluble viral-specific ligands on mucosal membranes, thereby reducing the cost and application frequency associated with the use of soluble viral-specific ligands to prevent viral infection.